Researchers at the University of Twente break new ground by successfully creating bone tissue “in vivo”, using embryonic stem cells. They imitated bone formation in embryos and children, which uses cartilage as a template. This new approach appears to be a promising way of repairing bone defects. This week, the researchers’ findings are presented in the Proceedings of the National Academy of Sciences (PNAS).
Previous attempts to create bone using embryonic stem cells were unsuccessful. In the lab, there was clear evidence that these stem cells were differentiating into the bone lineage “in vitro”, however this process stalled after implantation and no bone tissue was formed. Yet, this approach did lead to bone formation when cultured adult stem cells from bone marrow were used. This direct approach is, amongst others, involved in the formation of the bone found in the skull. The researchers at Twente have now adopted a different approach.
While searching for a suitable scaffold to use for cartilage tissue engineering with mouse embryonic stem cells, the researchers selected a ceramic material that is often used as bone void filler. Other materials appeared to be unsuitable or they made it difficult to locate the implanted cells. In the lab, mouse embryonic stem cells were seeded onto this ceramic material and induced into the developmental pathway leading to cartilage formation. Following implantation under the skin of a mouse, however, the cartilage tissue developed further, and was replaced by bone. Bone formation via cartilage as a template proved to be an efficient, if unexpected, approach. Furthermore, this is the way in which most of the bones in the embryo are formed. Bone growth in children also occurs via this process, known as endochondral ossification.
In their article, the researchers show that bone tissue is also formed in a bone defect. To demonstrate this, a scaffold with cells that had already formed cartilage, was implanted into a rat with a defect in its skull. Besides under the skin, bone was also formed in this bone defect. Therefore, this approach seems to be a promising new technique for repairing damaged bone.
Cross section showing “endochondral ossification”: bone formation on a cartilage template
The article entitled “Endochondral bone tissue engineering using embryonic stem cells” by Jojanneke Jukes, Sanne Both, Anouk Leusink, Lotus Sterk, Clemens van Blitterswijk and Jan de Boer was published in the 13 May 2008 edition of the Proceedings of the National Academy of Sciences of the United States of America (PNAS).